The long term objectives of this project are to develop new methods of asymmetric synthesis by gaining an understanding of the stereocontrol elements in existing methods, and applying what we have learned to the design of new reactions. We are primarily interested in reactions that form C-C bonds enantioselectively. Our approach focuses on the generation of chiral oxocarbenium ions, which can be considered activated ketones or aldehydes. these compounds may then undergo diastereoselective addition reactions, or Diels Alder reactions if the oxocarbenium ion is alpha-beta unsaturated, where the asymmetric induction is derived from the chirality of the oxocarbenium ion. In the first part of the proposal, we have unequivocally shown by a deuterium labeling experiment that the chiral acetal addition reactions discovered by W.S. Johnson proceed by way of an oxocarbenium ion. These reactions can display exceptional levels of diastereoselectivity, >300:1 in many cases, thus providing evidence that chiral oxocarbenium ions can provide high levels of asymmetric induction in addition reactions. We are extending our deuterated acetal studies to probe the mechanism of addition to acyclic acetals. We are also examining the activation of alpha-beta unsaturated carbonyl derivatives by their conversion to oxocarbenium ions. formation of the oxocarbenium ions in the Diels Alder reaction, allowing for new opportunities for controlling remote stereochemistry. We have proposed a short synthesis of the cholesterol biosynthesis inhibitor dihydrocompactin using this method, and are examining its scope. We also propose a catalytic variant where a chiral TMS ether is used in catalytic amounts to control the absolute stereochemistry in the Diels Alder reaction. Finally, we describe a chiral alpha-ferrocenyl cation which we hope will serve as an enantioselective catalyst for a variety of reactions. This reagent is similar to the trityl cation which has been shown to be an effective Lewis acid catalyst for numerous reactions including the aldol reaction, reduction of ketones with trialkylsilanes, 1,4 addition of silyl nucleophiles to alpha-beta unsaturated ketones and ester equivalents, and Diels Alder reactions. We describe an enantioselective synthesis of the catalyst precursor and have just begun to examine its reactivity as an asymmetric catalyst. The methods we discover can be used to synthesize a variety of molecules of medicinal interest.